Direct evidence for the role of neuropeptide Y in sympathetic nerve stimulation-induced vasoconstriction.
Neuropeptide Y (NPY) is a vasoconstrictor peptide and a cotransmitter with norepinephrine (NE) in sympathetic nerve terminals and is thought to be involved in sympathetic nerve stimulation (SNS)-induced vasoconstriction. Using BIBP-3226, a Y1 receptor selective antagonist, we examined this hypothesis in the isolated and perfused mesenteric vascular bed. SNS produced a frequency-dependent increase in perfusion pressure and concomitant overflow of NPY immunoreactivity in the perfusate. [Leu31,Pro34]NPY potentiated NE-induced and ATP-induced vasoconstriction, indicating the presence and biological action of Y1 receptors in this vascular bed. The potentiation effect of [Leu31,Pro34]NPY of the increase in perfusion pressure by NE, ATP, or SNS was prevented by BIBP-3226. In addition, SNS-induced vasoconstriction at both high and low frequencies was significantly attenuated by BIBP-3226 at a concentration that completely blocked the [Leu31,Pro34]NPY-induced potentiation of the NE- or ATP-induced vasoconstrictor effect. These results suggest that approximately 30% of vasoconstriction produced by SNS depends on NPY in the mesenteric vascular bed.
Han
S
S
Department of Pharmacological and Physiological Science, Saint Louis University Health Sciences Center, Missouri 63104, USA.
Yang
C L
CL
Chen
X
X
Naes
L
L
Cox
B F
BF
Westfall
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D007422:Intestines / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D001120:Arginine; D009638:Norepinephrine